516 posts · 447,425 views

I am a physician interested in clinical neuroscience research. I will use this blog to post more detailed analysis of recent studies in addition to my @WRY999 Twitter scientific reading log. I will also post some of my wildlife/sports photography. Aim to educate and amuse. Not selling anything.

William Yates, M.D.
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June 24, 2014
12:22 PM
356 views

E-cigarettes and Smoking Cessation

by William Yates, M.D. in Brain Posts

Electronic or e-cigarettes are a tobacco cigarette alternative that is growing in popularity.Proponents of e-cigarettes note the product contains no carbon monoxide, tar or other tobacco residue. The inhaled vapor in e-cigarettes is primarily nicotine.Additionally, some proponents of e-cigarettes declare the product is associated with reduction or cessation of tobacco-based cigarette use.Unfortunately, this is an area where public health trends come before scientific research data is collected. Few studies of the safety and effectiveness of e-cigarettes in smoking cessation have been published.One large study of electronic cigarettes and smoking cessation was completed and recently published in the journal Lancet.In this study, 657 smokers who wanted to quit were randomized one of three interventions: 16 mg nicotine e-cigarettes, 21 mg nicotine patches or placebo e-cigarette (nicotine free). Abstinence from cigarettes was verified by low concentrations of carbon monoxide.At the end of the study the cigarette abstinence rates for the three groups were:E-cigarettes: 7.3%Nicotine patch: 5.8%Placebo e-cigarettes: 4.1%These low rates of abstinence across all interventions were surprising to the researchers conducting the study. The overall low rates of abstinence reduced the statistical power of the study and no statistical difference across the three groups could be proven.Some smokers adopting e-cigarettes do not desire or intent to quit. In this group, a separate research question is what is the natural history of cigarette smoking in high-risk populations who start to use e-cigarettes?One small study looking at this question has been published in a group of 14 smokers with schizophrenia.In this study, smoking subjects were allowed to use ad lib an e-cigarette product. Subjects kept a diary of the number of tobacco cigarettes smoked.The results of this study found 2 of the 14 subjects quit tobacco cigarettes over the year long course of the study. An additional seven subjects reduced the number of cigarettes smoked by 50% or more by the end of the study. No adverse effects on schizophrenia symptoms levels were noted by participation in this study.With such a limited research database, it is really too early to make a recommendation about e-cigarettes as a tool for smoking cessation.There are quite a few studies in the pipeline that should inform smokers and clinicians. A query using the search term e-cigarette at the clinicaltrials.gov website produced 27 research study listings. Readers can access this list here.Readers with more interest in the two studies summarized here can access the abstracts and free full-text (schizophrenia study only) in the citations below.Photo of skimmer birds at sunset on South Padre Island, TX is from the author's files.Follow the author on Twitter at: WRY999Bullen, C., Howe, C., Laugesen, M., McRobbie, H., Parag, V., Williman, J., & Walker, N. (2013). Electronic cigarettes for smoking cessation: a randomised controlled trial The Lancet, 382 (9905), 1629-1637 DOI: 10.1016/S0140-6736(13)61842-5Caponnetto P, Auditore R, Russo C, Cappello GC, & Polosa R (2013). Impact of an electronic cigarette on smoking reduction and cessation in schizophrenic smokers: a prospective 12-month pilot study. International journal of environmental research and public health, 10 (2), 446-61 PMID: 23358230... Read more »

Bullen, C., Howe, C., Laugesen, M., McRobbie, H., Parag, V., Williman, J., & Walker, N. (2013) Electronic cigarettes for smoking cessation: a randomised controlled trial. The Lancet, 382(9905), 1629-1637. DOI: 10.1016/S0140-6736(13)61842-5

Caponnetto P, Auditore R, Russo C, Cappello GC, & Polosa R. (2013) Impact of an electronic cigarette on smoking reduction and cessation in schizophrenic smokers: a prospective 12-month pilot study. International journal of environmental research and public health, 10(2), 446-61. PMID: 23358230

June 23, 2014
10:52 AM
382 views

Varenicline for Smoking Cessation

by William Yates, M.D. in Brain Posts

Varenicline is a drug designed to assist smokers in cessation. It is marketed in the U.S. as Chantix.Varenicline is one of the first drugs to target the nicotine receptor. It is classified as a partial agonist, meaning it stimulates the nicotine receptor but to a weaker effect than nicotine itself.The mechanism of action of varenicline differs from that of another smoking cessation drug bupropion marked under trade name Zyban in the U.S.One concern with varenicline is the risk for psychiatric adverse effects including increase in anxiety ratings, increase in depression ratings and increased suicidality.There have been several studies over the last year that have expanded the knowledge base on varenicline. Here are four that I found from a search of PubMed.Clinical trial finds combining varenicline with bupropion improves quit ratesA randomized clinical trial of 506 subjects with nicotine dependence was completed across several setting in the U.S. At 12 weeks 53% of subjects in the combined varenicline/buproprion were smoking abstinent compared to 43% of those in the varenicline alone group.The was a slight increase in reported anxiety (7.2% vs 3.1%) and depression (3.6% vs 0.8%) in the combined therapy groups.Combined varenicline/bupropion helpful in those failing nicotine patch treatmentA group of 222 smokers who failed to respond to a nicotine patch trial were randomized to varenicline plus bupropion versus varenicline alone. Abstinence rates at 12 weeks were 39.8% for the combined drug group compared to 25.9% for the varenicline plus placebo group. This was a statistically significant advantage. Combined therapy appeared more helpful for male smokers and smokers with higher levels of nicotine dependence.Varenicline effective and safe in a sample of subjects with major depressionThe safety and effectiveness of varenicline in the original trials typically was studied in individuals without a psychiatric history of depression or suicidal ideation. Anthenelli and colleagues recruited a series of smokers with current major depression or a history of major depression for a varenicline study. Varenicline 1 mg twice daily was compared to placebo in a 12 week randomized controlled trial.Subjects with recent major depression had to be on a stable antidepressant treatment regimen for 2 months prior to enrollment.Varenicline treated subjects had higher abstinence rates at 9 to 12 weeks (35.9% vs 15.6%). Importantly, the varencline treated group at risk for depression showed no increase in suicidal ideation, anxiety or depression during active treatment.Belgium study finds predictors for success with vareniclineBoudrez and colleagues examined a cohort of varenicline treated subjects. The time to first cigarette on awakening was found to be related to smoking cessation rates. At week 12, the odds ratio for time to first cigarette and abstinence was 0.69 (95% confidence interval 0.50 to 0.94). This suggests varenicline as more effective in those with shorter duration to first cigarette an indicator of nicotine dependence.This study also found use of behavioural support predicted higher quit rates in smokers.CommentaryThese four studies lend support to the effectiveness and safety of varenicline in smoking cessation drug therapy. Combining varenicline with the antidepressant bupropion may boost quit success rates.These results also support use of varenicline as a treatment option for those with a history or current depression. This group appears to have somewhat lower rates of success compared to non-depressed sample groups.Clinical trials for those with nicotine dependence and a psychiatric diagnosis are important. Several psychiatric disorders have increased rates of smoking and nicotine dependence. It is probably best to consider smoking cessation drug treatment during periods of remission and stability of the primary psychiatric diagnosisReaders with more interest in this topic can access the abstracts by clicking on the links below. The Anthenelli et al citation has a link to a free full text manuscript.Disclosure: The author has no financial association with any pharmaceutical company including the maker of varenicline in the U.S. This post topic was selected and completed by the author alone with no payment.Follow the author on Twitter at WRY999Photo of American bittern in South Padre Island, TX is from the author's files.Ebbert JO, Hatsukami DK, Croghan IT, Schroeder DR, Allen SS, Hays JT, & Hurt RD (2014). Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial. JAMA : the journal of the American Medical Association, 311 (2), 155-63 PMID: 24399554Rose JE, & Behm FM (2014). Combination Treatment With Varenicline and Bupropion in an Adaptive Smoking Cessation Paradigm. The American journal of psychiatry PMID: 24934962Anthenelli RM, Morris C, Ramey TS, Dubrava SJ, Tsilkos K, Russ C, & Yunis C (2013). Effects of varenicline on smoking cessation in adults with stably treated current or past major depression: a randomized trial. Annals of internal medicine, 159 (6), 390-400 PMID: 24042367... Read more »

Ebbert JO, Hatsukami DK, Croghan IT, Schroeder DR, Allen SS, Hays JT, & Hurt RD. (2014) Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial. JAMA : the journal of the American Medical Association, 311(2), 155-63. PMID: 24399554

Rose JE, & Behm FM. (2014) Combination Treatment With Varenicline and Bupropion in an Adaptive Smoking Cessation Paradigm. The American journal of psychiatry. PMID: 24934962

Anthenelli RM, Morris C, Ramey TS, Dubrava SJ, Tsilkos K, Russ C, & Yunis C. (2013) Effects of varenicline on smoking cessation in adults with stably treated current or past major depression: a randomized trial. Annals of internal medicine, 159(6), 390-400. PMID: 24042367

Boudrez H, Hoengenaert JP, Nackaerts K, Messig M, & Metcalfe M. (2013) Predictors of quit success in Belgian participants of a varenicline observational smoking cessation study. Acta clinica Belgica, 68(1), 37-42. PMID: 23627193

June 20, 2014
12:07 PM
410 views

Maternal Smoking and Child Conduct Disorder Risk

by William Yates, M.D. in Brain Posts

Conduct disorder is a serious behavioral disorder of childhood characterized by aggression, destruction of property, lying, theft and violation of rules.A significant number of children with conduct disorder go on to adult antisocial personality disorder.Conduct disorder is known to have genetic as well as environmental risk factors.Darya Gaysina from the United Kingdom and colleagues recently published a review of maternal smoking during pregnancy and offspring conduct problems.This review examined three independent studies including:The Christchurch Health and Development StudyThe Early Growth and Development StudyThe Cardiff Invitro Fertilization Study These studies combined adoption study designs with biological children designs to examine risk for childhood disorders. This allowed for comparison of results for children raised by genetically related and genetically unrelated mothers.Maternal smoking status in these studies was grouped into three categories, 0 cigarettes/day, 1-9 cigarettes per day and 10 or more cigarettes per day.Children were rated for conduct problems between the ages of four and seven years.The research design of these studies included controlling for important covariates including child gender, ethnicity, birth weight, maternal age at birth, breast feeding status, maternal education, socioeconomic status and parenting style.Across all the three studies similar findings and strength of associations were found. Maternal smoking increased risk of childhood conduct disorder with odds ratios estimated of between 2 and 4 fold.This effect was found for both the children raised by their biological mother and those adopted children raised by mothers who were not there biological mothers.This last finding helps disentangle maternal smoking effects from maternal child rearing effects and supports a specific link to environmental effects from maternal smoking. The limitations of these studies include difficulty sorting out potential effects of maternal smoking during pregnancy versus effects of passive smoking ("second-hand smoke") exposure. Additionally genetic risk for maternal smoking may overlap with genetic risk for conduct disorder.I have previously collaborated with Dr. Remi Cadoret in adoption study design research on aggression and conduct disorder. We found significant contributions of genetic factors to conduct disorder.Additionally, our research found a significant interaction between genetic and environmental risk. Children with genetic risk for conduct disorder experienced the most negative effect of adverse home environment, i.e. marital discord, divorce, parental mental health or substance abuse diagnoses.It would be interesting to evaluate whether exposure to maternal smoking is more adverse for children who also have a genetic risk for conduct disorder.Readers with more interest in this research can access the free full-text article by clicking on the PMID link in the reference below.Photo of sculpture from the Illumnia collection outside the CenturyLink Arena in Omaha, Nebraska is from the author's files. Sculpture is by the artist Matthew Placzek.Follow the author on Twitter at WRY999Gaysina D, Fergusson DM, Leve LD, Horwood J, Reiss D, Shaw DS, Elam KK, Natsuaki MN, Neiderhiser JM, & Harold GT (2013). Maternal smoking during pregnancy and offspring conduct problems: evidence from 3 independent genetically sensitive research designs. JAMA psychiatry, 70 (9), 956-63 PMID: 23884431 Cadoret RJ, Yates WR, Troughton E, Woodworth G, & Stewart MA (1995). Genetic-environmental interaction in the genesis of aggressivity and conduct disorders. Archives of general psychiatry, 52 (11), 916-24 PMID: 7487340... Read more »

Gaysina D, Fergusson DM, Leve LD, Horwood J, Reiss D, Shaw DS, Elam KK, Natsuaki MN, Neiderhiser JM, & Harold GT. (2013) Maternal smoking during pregnancy and offspring conduct problems: evidence from 3 independent genetically sensitive research designs. JAMA psychiatry, 70(9), 956-63. PMID: 23884431

Cadoret RJ, Yates WR, Troughton E, Woodworth G, & Stewart MA. (1995) Genetic-environmental interaction in the genesis of aggressivity and conduct disorders. Archives of general psychiatry, 52(11), 916-24. PMID: 7487340

June 19, 2014
11:20 AM
410 views

Smoking and Abnormal Brain Pleasure Response

by William Yates, M.D. in Brain Posts

Smoking cessation in those with nicotine dependence is one of the most difficult challenges for patients and their clinicians.Research targeting the neurobiology of smoking cessation provides hope for designing more effective treatments for nicotine dependence.Takeshi Isomura along with colleagues in the U.S. and Japan recently summarized recent findings in the brain pleasure response in nicotine dependence.The brain ventral striatum region is known to be key in nearly all sensations of pleasure.Isomura and colleagues note research supports specific changes in reward response among nicotine dependent individuals.During the process of developing nicotine dependence, the brain reward circuitry develops an adaptive drug-related brain response to cues.In smokers, this adaptation produces abnormally elevated responses to smoking cues in the pleasure circuitry involving the ventral striatum, orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (VMPFC). This sensitization or turbocharging of the brain's response to a specific drug cue contributes to the difficulty in discontinuing drug use.However, another phenomenon appears to be important to developing nicotine and drug dependence. This phenomenon is the adaptation of the brain's pleasure response to non-drug related stimuli.Brain imaging studies using fMRI in adolescents show the potential for smoking only a few cigarettes to modify the pleasure response.Research by Peters and his group demonstrated a reduction in ventral striatum response to a monetary incentive reward in adolescents who had smoked compared to adolescents who had not smoked. The reduction in pleasure response to non-drug cues was greatest in those who smoked regularly but could be demonstrated even in those who had smoked as few as 5 to 10 cigarettes in their lifetime.There are two possible explanations for this finding. Either lowered non-drug pleasure response increases risk for smoking or smoking reduces the responsivity of the ventral striatum.The Isomura notes that heightened pleasure response to nicotine and reduced pleasure response to other rewards may contribute to a cognitive distortion in smokers.This distortion produces cognition that something like "Smoking is my only source of pleasure and things that others enjoy, for example hobbies are not pleasurable for me" This type of cognitive distortion is substance abusers has been described by Aaron Beck and other pioneers in the cognitive behavioral treatment of addiction.Isomura notes the effect of even small numbers of cigarettes in adolescents is like the "Paradise Lost" phenomenon described with the fall of Adam and Eve. Their analogy posits teenagers who begin smoking find lost pleasure (paradise) in typically pleasurable activities. Like Adam and Eve, once the forbidden apple is is consumed, it is impossible for the teenage smoker to return to the Garden of Eden present before smoking.Smoking cessation treatments may need to focus more on re-establishing non-nicotine reward responses. This type of intervention, may provide greater chances for combating the addictive brain response to nicotine.Readers with more interest in this topic can find the free full-text manuscript by clicking on the link in the Isomura reference below.Photo of sculptures outside CenturyLink arena in Omaha, Nebraska is from the author's files.Follow the author on Twitter WRY999Isomura T, Suzuki J, & Murai T (2014). Paradise Lost: The relationships between neurological and psychological changes in nicotine-dependent patients. Addiction research & theory, 22 (2), 158-165 PMID: 24719610Peters J, Bromberg U, Schneider S, Brassen S, Menz M, Banaschewski T, Conrod PJ, Flor H, Gallinat J, Garavan H, Heinz A, Itterman B, Lathrop M, Martinot JL, Paus T, Poline JB, Robbins TW, Rietschel M, Smolka M, Ströhle A, Struve M, Loth E, Schumann G, Büchel C, & IMAGEN Consortium (2011). Lower ventral striatal activation during reward anticipation in adolescent smokers. The American journal of psychiatry, 168 (5), 540-9 PMID: 21362742... Read more »

Isomura T, Suzuki J, & Murai T. (2014) Paradise Lost: The relationships between neurological and psychological changes in nicotine-dependent patients. Addiction research , 22(2), 158-165. PMID: 24719610

Peters J, Bromberg U, Schneider S, Brassen S, Menz M, Banaschewski T, Conrod PJ, Flor H, Gallinat J, Garavan H.... (2011) Lower ventral striatal activation during reward anticipation in adolescent smokers. The American journal of psychiatry, 168(5), 540-9. PMID: 21362742

June 10, 2014
10:54 AM
485 views

Smoking During Pregnancy and Fetal Growth

by William Yates, M.D. in Brain Posts

Smoking cigarettes during pregnancy is linked to a variety of adverse effects including increased perinatal mortality, gestational bleeding and placenta abruptio and placenta previa.Newborns of smoking mothers weigh less than newborns of nonsmoking mothers.The specific distribution of target organ growth impairment with maternal smoking is less well studied.Devasuda Anblagan and colleagues in the United Kingdom and Canada recently published a study of fetal organ growth in smoking mothers.Using magnetic resonance imaging (MRI), a technique without radiation exposure, they estimated fetal growth parameters during pregnancy.Smoking mothers and a control group of nonsmoking mothers consented to a fetal MRI at between 22 and 27 weeks gestation (time 1), followed by a second image at between 33 and 38 weeks gestation (time 2).Total fetal volumes as well as specific organ volumes for brain, lung, kidney, liver and placenta were estimated. This was done by an research team member blind to the smoker vs nonsmoker status of each fetus. Fetal size estimates were done using two validated region of interest techniques from the MRI images.The key findings (smokers vs nonsmokers) from the study were:Fetal brain volumes did not differ at time 1 (69 cubic centimeters vs 77 cubic centimeters) but were significantly smaller in smokers at time 2 (246 cubic centimeters vs 278 cubic centimeters)Total fetal volume, kidney volume and lung volumes were significantly reduced at time 1 and time 2 in those with smoking mothersPlacental volumes were significantly smaller at time 1 (280 cubic centimeters vs 470 cubic centimeters) although this gap closed significantly by time 2Smoking status did not appear to significantly reduce the liver volume estimates at time 1 or time 2The most striking finding is the gap in placenta size at time 1 in this study with the smoking mother placental size being only 60% of the volume of the nonsmoking mothers.The authors note some deficits in fetal growth may be minimized by later infant and childhood catch-up growth.But they also note their previous research found a reduction in brain corpus callosum volume in female adolescents exposed to cigarette smoke in utero.The authors conclude the brain and kidney appear most vulnerable to the effects of exposure to nicotine and carbon monoxide in utero.These findings add to the need for continued public health effects to integrate smoking cessation programs in the health care of young women prior to pregnancy.Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of an osprey with large mouth bass is from the author's files.Follow the author on Twitter at WRY999.Anblagan D, Jones NW, Costigan C, Parker AJ, Allcock K, Aleong R, Coyne LH, Deshpande R, Raine-Fenning N, Bugg G, Roberts N, Pausova Z, Paus T, & Gowland PA (2013). Maternal smoking during pregnancy and fetal organ growth: a magnetic resonance imaging study. PloS one, 8 (7) PMID: 23843995... Read more »

Anblagan D, Jones NW, Costigan C, Parker AJ, Allcock K, Aleong R, Coyne LH, Deshpande R, Raine-Fenning N, Bugg G.... (2013) Maternal smoking during pregnancy and fetal organ growth: a magnetic resonance imaging study. PloS one, 8(7). PMID: 23843995

June 9, 2014
11:04 AM
503 views

Smoking Linked to Brain White Matter Dysfunction

by William Yates, M.D. in Brain Posts

Tobacco smoking and nicotine dependence produce harmful effects on the brain.Some of these effects are related to direct effects on vascular health. Vascular changes seen with smoking are known to contribute to increased risk for stroke and dementia.Advances in brain imaging techniques allow for more direct study on smoking's effect on specific brain structures.Diffusion tensor imaging (DTI) is a relatively recent imaging tool allowing for study of brain white matter function.Brain white matter contains the brain wiring neurons connecting gray matter regions across the brain. White matter integrity is essential for cognition tasks requiring use of a brain circuit.Wakako Umene-Nakano and colleagues in Japan imaged 18 smokers and age-matched controls using DTI.Smokers and non-smokers did not differ on measures of total gray matter volume or total white matter volume.However, when they examined the DTI parameters, smokers showed a statistically significant reduction in fractional anisotropy involving the entire white matter region known as the corpus callosum.Interestingly, other white matter tracts in the brain did not show significant changes in fractional anisotropy with smoking.There are three key measures of white matter function in DTI: fractional anisotropy, radial diffusivity and axial diffusivity. Smokes in this study showed only dysfunction in the fractional anisotropy measure.Fractional anisotropy reduction in smokers was negatively correlated (r=.52, p=0.023) with a smoking history measure (number of cigarettes smoked per day). Looked at another way, this direction of correlation indicates more dysfunction with higher number of cigarettes smoked per day.The authors note reduction in fractional anisotropy in the corpus callosum and is: "likely the manifestation of axonal damage and disrupted myelin integrity in the region."The corpus callosum runs the entire length of the brain connection right and left brain hemisphere regions (see figure).Dysfunction in white matter integrity in the corpus callosum could lead to a variety of cognitive deficits. Some studies have demonstrated impaired executive function and impaired visual memory function in smokers. White matter dysfunction could contribute to these types of cognitive deficits.The authors note that smoking and heavy alcohol consumption often go together and they could not completely rule out a contribution of alcohol to their primary finding.Readers with more interest in this research are directed to the free full-text link that can be accessed by clicking on the PMID link portion of the citation below.Figure of corpus collosum white matter tracts in colored fibers is an iPad screen shot from the Brain Tutor app.Follow the author on Twitter: WRY999Umene-Nakano W, Yoshimura R, Kakeda S, Watanabe K, Hayashi K, Nishimura J, Takahashi H, Moriya J, Ide S, Ueda I, Hori H, Ikenouchi-Sugita A, Katsuki A, Atake K, Abe O, Korogi Y, & Nakamura J (2014). Abnormal white matter integrity in the corpus callosum among smokers: tract-based spatial statistics. PloS one, 9 (2) PMID: 24516568... Read more »

Umene-Nakano W, Yoshimura R, Kakeda S, Watanabe K, Hayashi K, Nishimura J, Takahashi H, Moriya J, Ide S, Ueda I.... (2014) Abnormal white matter integrity in the corpus callosum among smokers: tract-based spatial statistics. PloS one, 9(2). PMID: 24516568

June 4, 2014
10:12 AM
475 views

Types of Mathematics Learning Disorders

by William Yates, M.D. in Brain Posts

Learning mathematics is a complex process that forms a key element in modern education.Significant mathematics learning difficulties emerge in 5 to 10 per cent of all elementary and secondary education students.Struggling to acquire skills in mathematics is more than a single deficit and appears to involve multiple cognitive skills.Giannis Karagiannakis and colleagures recently summarized what is known about mathematics learning disorders and proposed four subtypes. I will summarize these subtypes based upon his manuscript:Core number subtype: This subtype represents a key early skill for learning mathematics. It denotes the ability to accurately generate an internal representation of quantity and understand different representations of quantity, i.e. analog-verbal-Arabic. It also includes difficulty understanding basic symbols of arithmetic operation symbols. Memory subtype: This subtype reflects a deficit in working memory and semantic memory. Children and adults with this type of mathematical learning disorder have problems retrieving numerical facts, performing mental calculations. Additionally, because of memory deficits, this subtype struggles with keeping track of steps in a multistage arithmetic problem.Reasoning subtype: This proposed subtype shows deficits in executive functions such as planning and decision-making. Executive function skills come in to play with mathematical problems include complex algorithms, if-then conditional probability and decision selection.Visual-Spatial subtype: In this subtype there is a deficit in visuospatial skills resulting in problems with the spatial representation of numbers. Learners with deficits in this subtype will struggle with tasks such as placing numbers on a number line, geometric representations and rotations and the interpretation of numerical information presented in graphs or tables.The authors note these types of cognitive skills utilize both the left and right brain hemispheres. This suggests the potential for specific genetic and environmental risks for the specifity sub-types of mathematics learning disorders.The authors also note, that students with mathematics learning problems show receive neuropsychological testing for each of the four outlined sub-types.Such testing might more accurately determine whether students a single type of disorder or a more complex disorder involving multiple sub-types.This information might help direct individualized teaching strategies to correct or limit mathematical cognitive deficits.Readings with more interest in this topic can access the free full-text manuscript by clicking on the PMID link below.The mathematical figure in this post is from a Wikipedia Commons file uploaded by OgreBot.Readers can follow the author on Twitter at WRY999Karagiannakis G, Baccaglini-Frank A, & Papadatos Y (2014). Mathematical learning difficulties subtypes classification. Frontiers in human neuroscience, 8 PMID: 24574997... Read more »

Karagiannakis G, Baccaglini-Frank A, & Papadatos Y. (2014) Mathematical learning difficulties subtypes classification. Frontiers in human neuroscience, 57. PMID: 24574997

June 3, 2014
11:14 AM
551 views

Executive Cognition in Autism Sprectrum Disorder

by William Yates, M.D. in Brain Posts

Executive functions (EF) of the brain are processes used to make complex decisions and plans.Deficits in EF can produce significant impairment in the ability to successfully many daily life challenges.EF are felt to be primarily a reflection of workings of the frontal lobe although additional brain regions contribute this cognitive skill.Simonetta Panerai and colleagues from Italy recently examined the key components of EF in a group of children with autism sprectrum disorder (ASD). They administered a series of executive function tests to children with ASD and controls and their parents:Planning skills: Tower of London and Clock Drawing TestMental flexibility: Wisconsin Card Sorting testResponse inhibition: Stroop test, Go-no-Go trialGenerativity: Test of verbal fluency based on category and phenome cuesEcological: Parental rating scale with eight subcategories and three indices (behavioral regulation, metacognition and global executive composite)Adaptive Functioning: Parental interview addressing child's personal, social and communication skillsThe key findings from their study were:The entire group of children with ASD showed deficits in EF most notable in the flexibility, planning, behavioral regulation and monitoring metacognitionThese deficits were present in ASD children who were high functioning as well as ASD children with some intellectual impairmentEF deficits correlated with measures of real life problems in adaptability and socializationThe authors note their findings support a distinct profile of executive function deficits in children with ASD that appears independent of level of intellectual.These deficits appear to contribute to some of the problems experienced by children with ASD including impaired flexibility, poor planning and socialization issues. The clinical implications of these findings include:Neuropsychological testing of EF in ASD is an important clinical assessment toolInterventions to address EF deficits may play an important role in multidisciplinary treatment planningA key limitation of this study is the relatively small sample size of ASD children (N=27) with only eleven children in the high-functioning ASD category. This small sample size issue points to the need for replication in other larger sample groups.Readers with more interest in this research can access the free full-text article by clicking on the PMID link in the citation below.Photo of fish from the Oklahoma Aquarium is from the author's files.Follow the author on Twitter @WRY999Panerai S, Tasca D, Ferri R, Genitori D'Arrigo V, & Elia M (2014). Executive Functions and Adaptive Behaviour in Autism Spectrum Disorders with and without Intellectual Disability. Psychiatry journal, 2014 PMID: 24829905... Read more »

Panerai S, Tasca D, Ferri R, Genitori D'Arrigo V, & Elia M. (2014) Executive Functions and Adaptive Behaviour in Autism Spectrum Disorders with and without Intellectual Disability. Psychiatry journal, 941809. PMID: 24829905

June 2, 2014
11:52 AM
474 views

Brain Resting Connectivity Deficits in Autism

by William Yates, M.D. in Brain Posts

Resting connectivity is a measure of brain circuitry obtained by functional magnetic resonance imaging (fMRI).This technique is relatively new but there is emerging evidence of the potential value in research and clinical assessment.Research in brain connectivity includes looking for distinct patterns in brain disorders compared to health controls.One such type of study in autism has been published by a group of Japanese researchers.Takashi Itahashi and colleagues recruited 46 adult subjects with autism spectrum condition (ASC) between the ages of 18 and 55. A control group of subjects were recruited without a history of any mental disorders.The autism spectrum subjects had a mean IQ estimate of 105 compared to 108 in the control group.In resting connectivity studies, subjects are imaged without a specific cognitive task. The fMRI analysis is complicated but looks for correlated regions where there is synchronized signaling suggesting connectivity. Specific brain regions known to be involved in brain connectivity known as hub nodes can be studied and measured.The key findings from this study included the following:The ASC group showed a tendency for more randomized or non-organized signalingHub nodes in the superior temporal gyrus, right dorsolateral prefrontal cortex and precuneus were impaired in ASC compared to controlsConnectivity metrics in the anterior cingulate cortex showed a negative correlation with a measure of autism spectrum severity (Autism-Sprectrum Quotient score)The authors note brain superior temporal region plays a key role in social perception. Impairment of connectivity involving the superior temporal gyrus could contribute to social perceptual impairments common in ASC.The authors also note the pairing of genetic data with fMRI findings might be a valuable next step in understanding ASC. They comment:Molecular basis of ASC is associated with many of the synaptic cell-adhesion molecules, including neurexins, neuroligins, and cadherins, all of which play important roles in determining aspects of neural connections including synaptic formation and axonal guidance.This study did not focus on using brain resting connectivity to improve diagnostic accuracy in ASC or other psychiatric disorders. This is an important potential avenue for the technology.Additionally, we are beginning to see research looking at changes in connectivity with specific therapeutic interventions. This type of research may aid in designing the most effective interventions and examining individual responsiveness to treatment.Readers with more interest in this topic can access the free full-text manuscript by clicking on the reference link below.The figure in this post is an iPad screen shot from the app 3D Brain from the author's files.Follow the author on Twitter @WRY999Itahashi T, Yamada T, Watanabe H, Nakamura M, Jimbo D, Shioda S, Toriizuka K, Kato N, & Hashimoto R (2014). Altered network topologies and hub organization in adults with autism: a resting-state FMRI study. PloS one, 9 (4) PMID: 24714805... Read more »

Itahashi T, Yamada T, Watanabe H, Nakamura M, Jimbo D, Shioda S, Toriizuka K, Kato N, & Hashimoto R. (2014) Altered network topologies and hub organization in adults with autism: a resting-state FMRI study. PloS one, 9(4). PMID: 24714805

May 29, 2014
10:45 AM
441 views

The Aging Political Brain: Hillary's Advantage

by William Yates, M.D. in Brain Posts

There has been significant public discussion on the topic of politicians running for office at an older age. I wanted to add a few comments to this discussion from a neuroscience perspective on the aging brain.I think there are three key elements in this topic. The first is pretty universal effect of age to produce a reduction in psychomotor speed. The graph above shows norms for the completion of the Trails B Test by age. This test involves connecting an alternating number/letter series of dots in a timed test. The norms demonstrate that psychomotor speed as assessed in this test is relatively preserved until around 70 years of age and then decreases significantly and progressively.How this task might effect day-to-day tasks for presidents and congressmen and women is unclear. However, it is a non-trivial issue that is an important aspect of the aging brain.A second important topic of discussion is increased risk of incident cognitive decline and dementia. Risk of dementia increases progressively with age. Using data from a U.S. population based survey, the rates of incident dementia (all types) rises from 4.3 per 1000 individuals for those age 65-69, to 12.0 per 1000 for those age 70-74 and 21.1 for those age 75 to 79.The rates of incident dementia are somewhat lower in women than in men by about 20%. Additionally, elected politicians typically have high educational levels, a factor that is know to reduce risk and potentially delay the timing of cognitive decline with age.However, using the rates from the U.S., for an elderly politician elected president, the rate of incident cognitive impairment and dementia is also nontrivial. Based on my review of the data a president elected at age 70+ would have somewhere between a 5 and 15% chance of clinically significant cognitive impairment over the course of an 8 year presidential cycle.Finally, there is the issue of mortality risk. Mortality risk climbs steadily with age and becomes a nontrivial issue for candidates approaching 70 and older. The National Journal recently published an article stating that Hillary Clinton's age should not be considered a factor for mortality risk. They calculated that for her age at inauguration in 2016 she would have a life expectancy of 17 more years.I don't contest the projection of life expectancy in their article, but it does neglect this issue of risk of death before one's projected life expectancy is met. Not all 69 year old women will live 17 more years. Some will live shorter, some longer.The more appropriate estimate might be what is the risk of an elderly politician dying during an 8 year term in office.Using actuarial data from the Social Security Administration, I have put together a year by year table of estimated mortality risk for older men and women in the U.S.These estimates are shown along with past, current and potential future presidents ages. The estimated 8 year mortality for a 69 year old woman in the U.S. is 17%. Note that this estimated risk in women is significantly lower than a similarly aged male who has about a 27 to 30% 8 year mortality risk.These risks are significantly increased compared to younger presidents. For example, for a male age 48 (the age of Barack Obama at his first inauguration) the 8 year mortality risk is only 5% and the incident dementia risk is less than 1%The 8 year mortality risk for men in the U.S. jumps to nearly 40% for men who 74 years of age (the age of Joe Biden if elected president in 2016).Exact estimates for specific individuals or candidates cannot be precisely made. Nevertheless, the Social Security Administration data is informative and provides a ball park guide to relative risks.The dementia and mortality data show older women have a more favorable brain aging and mortality outcomes than men. I think this age-related gender advantage provides older women an opportunity to serve in elected office later in the human life-cycle.In the case of Hillary Clinton, a lower gender-related risk for cognitive impairment and mortality may be an advantage. This is particularly true when contrasted against other male candidates in the same (or older) age range.Obviously the potential impact of age and it's effect on the brain is only one issue of importance when selecting and voting for candidates for public office. The aging issue is nontrivial but may be less an issue if there are other factors supporting the value of older candidates, i.e. experience.CandidateHillary ClintonDonald TrumpJoe BidenRonald ReaganBarack ObamaBirth Date10/26/19476/14/194611/20/19422/6/19118/4/1961Age at Inaug69.270.674.269.948... Read more »

Tombaugh, T. (2004) Trail Making Test A and B: Normative data stratified by age and education. Archives of Clinical Neuropsychology, 19(2), 203-214. DOI: 10.1016/S0887-6177(03)00039-8

Ganguli, M., Dodge, H., Chen, P., Belle, S., & DeKosky, S. (2000) Ten-year incidence of dementia in a rural elderly US community population: The MoVIES Project. Neurology, 54(5), 1109-1116. DOI: 10.1212/WNL.54.5.1109

May 28, 2014
11:32 AM
460 views

Physical Abnormalities in Adults with Autism Spectrum

by William Yates, M.D. in Brain Posts

In a previous post, I reviewed a study of minor physical abnormalities in a group of children with autism.This study found that children with autism were more likely to show a variety of physical features including a gap between the large and second toe, facial asymmetry, a high arched palate and attached ear lobes.A more recent Swedish study has been published examining physical features of adults with autism spectrum disorder (ASD).In this study, Irina Manouilenko and colleagues used a scale that is specifically designed to assess minor physical abnormalites or MPAs.This scale, known as the Waldrop scale is composed of 16 items resulting in a total score ranging from 0 to 25.The scale can be assess from detailed photographs of an individuals face, mouth, hand and feet.In this Swedish study, expert clinicians blindly rated photographs of 50 adults subjects with autism spectrum disorder and 53 controls on the Waldrop scale.Autism spectrum disorder in the cases was made following extensive interviews, neuropsychological testing, record review and a direct clinical interviews with expert psychiatrist.All ASD subjects had IQ testing that was within the normal range.The primary findings from the study included the following:The distribution of MPAs in ASD was bimodal--the lower curve overlapped with the control distribution but a distinct group of cases had higher scoresASD subjects were more likely than controls to have increased head circumference (16% vs 4%) fine hair with "hair soon awry" (24% vs 8%) and a single palmar crease (14% vs 0%)ASD subjects were less likely to show a moderately curved fifth finger (4% vs 19%)Mean scores on the Waldrop scale were calculated for six topographical regions including head, eyes, ears, mouth, hand and feet.The higher mean scores in the ASD group was primarily composed of higher scores in the head and ears subscale domains.Higher MPAs scores correlated with lower overall functioning as assessed by the Global Assessment of Function scale (GAF).The authors note that head and facial fetal development happens concurrently with brain development. They propose that abnormal head and facial development features may be a biomarker for brain disorders including ASD.This study is consistent with other studies in children with autism. Detailed external physical assessment may play a role in understanding the genetics and pathophysiology of brain disorders such as ASD.Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link below.Follow the author on Twitter at WRY999Photo of male cardinal is from the author's files.Manouilenko I, Eriksson JM, Humble MB, & Bejerot S (2014). Minor physical anomalies in adults with autism spectrum disorder and healthy controls. Autism research and treatment, 2014 PMID: 24782925... Read more »

Manouilenko I, Eriksson JM, Humble MB, & Bejerot S. (2014) Minor physical anomalies in adults with autism spectrum disorder and healthy controls. Autism research and treatment, 743482. PMID: 24782925

May 21, 2014
01:04 PM
371 views

Testing Boosts Memory: Brain Region Involvement

by William Yates, M.D. in Brain Posts

Taking tests provides one method to assess the level of learning in a subject matter.Testing may also be an aid to improving memory and learning.Studies support periodic testing as a superior strategy to restudying learned material. Testing may promote learning by activating memory retrieval.The mechanism for the beneficial effects of testing on memory have received limited research attention.However, a recent fMRI study provides some insight into the specific brain regions involved in memory improvement with testing.Xiaonan L. Liu along with colleagues in the U.S. and China studied a group of young subjects using fMRI. The key elements of the study included the following elements:Subjects: Twenty healthy female and male graduate students from Capital Medical University in Beijing, ChinaProcedure: Subjects were given 90 pairs of Chinese words and then given tests of learning along with an opportunity to spend time restudying the word pairs. Imaging and Analysis: Subjects underwent 3.0 Tesla fMRI scanning during the procedure. Brain region activation patterns were compared for learning via retrievel (testing) and during restudy. Brain regions activated specifically with learning via retrieval and learning during restudy were identified by multivariate analysis.Regions known to be active in restudy learning or memory encoding were confirmed in the current study including the left prefrontal cortex, the left posterior parietal cortex and the hippocampus.The research team identified two regions activated specifically with retrieval (testing) learning. These two regions were the right prefrontal cortex and the right posterior parietal cortex.The authors note the right prefrontal cortex has been linked to working memory processes and cogntive control during memory retrieval. They comment:"Conceivably, the activation of the right PFC (prefrontal cortex) during retrieval is responsible for stronger association formation and better learning than what typically occurs during study".This study adds to our understanding how testing may activate unique brain regions in the learning process.From a practical standpoint, teachers can use testing not only as an assessment tool, but as a memory enhancement strategy. Use of restudy techniques alone appears to ignore key brain regions and mechanisms that improve memory.Readers with more interest in this topic can access the free full-text article by clicking on the citation link below.Figure highlighting the brain prefrontal cortex region is a screen shot of iPad app 3D Brain from the authors files.Liu XL, Liang P, Li K, & Reder LM (2014). Uncovering the neural mechanisms underlying learning from tests. PloS one, 9 (3) PMID: 24647122... Read more »

Liu XL, Liang P, Li K, & Reder LM. (2014) Uncovering the neural mechanisms underlying learning from tests. PloS one, 9(3). PMID: 24647122

May 13, 2014
11:05 AM
396 views

Sleep Manipulation to Enhance Cognition

by William Yates, M.D. in Brain Posts

In the next series of posts, I will focus on research related to learning, learning disabilities and education.Sleep is known to play a key role in consolidation of memories and and learning.However, there has been relatively little discussion of how the effect of sleep on learning might be enhanced.Susanne Diekelmann reviewed this issue in a recent manuscript published in the journal Frontiers in Systems Neuroscience.In this review, two theories for sleep enhancement of memories are proposed:Active system consolidation theory: In this theory, "new memories become reactivated and reorganized on the the system-level during sleep". In this theory, neuronal connections related to a memory are "potentiated and thereby strengthened during periods of sleep.Synaptic homeostasis theory: This theory notes synaptic connections are generally depotentiated during sleep but that recent memories may be relatively spared. This might lead to a increase in retention of recent memories.Sleep timing may be used to aid in memory and cognition. Sleep before a learning task appears to enhance encoding. Sleep after a learning task appears to promote consolidation of recent memories for subsequent retrieval.Diekelmann reviews three specific methods of sleep manipulation that deserve further study:Manipulation of memory reactivation during sleep: Diekelmann notes that odor clues seem to have a beneficial effect on memory. Nocturnal presentation of an odor linked to a learning task during slow wave sleep increases memory retention of the task. Nocturnal presentation of auditory stimuli linked to a learning task also appears to increase retention.Manipulation of sleep-specific oscillations: Slow wave sleep appears to have the strongest effect on memory consolidation. Manipulation of sleep to increase the amount of time in slow wave sleep may provide enhanced cognition. Slow wave sleep is increased by a technique known as electrical transcranial direct current stimulation (tDCS). Short auditory stimulation at specific frequencies increases slow wave oscillations in the human brain. tDCS and auditory stimulation studies show enhancement of memory for learned word pairs.Manipulation of neurotransmitter systems: Several neurotransmitter systems appear involved in sleep. Initial studies support specific drug (neurotransmitter system) effects on cognition including: reboxetine (noradrenaline), D-cycloserine (glutamine), pramipexole (dopamine), and GABA (zolpidem). Acetylcholine and cortisol also are involved in nocturnal memory consolidation and may be potentially manipulated to enhance cognition.Diekelmann notes the manipulation of sleep for enhancement of cognition is not without potential adverse effects. The practical implementation of these techniques has not yet been resolved. Ethical issues are also important to consider.However, manipulation of sleep to enhance cognition and restore cognition in disorders such as depression and PTSD is a promising clinical strategy. We are likely to see increasing attention to this research and clinical topic.Readers with more interest in this topic can access the free full-text manuscript by clicking on the link below.Photo of a lorikeet is from the author's files.Follow the author on Twitter at WRY999.Diekelmann, S. (2014). Sleep for cognitive enhancement Frontiers in Systems Neuroscience, 8 DOI: 10.3389/fnsys.2014.00046... Read more »

Diekelmann, S. (2014) Sleep for cognitive enhancement. Frontiers in Systems Neuroscience. DOI: 10.3389/fnsys.2014.00046

May 7, 2014
11:01 AM
464 views

Sleep, Inflammation and Risk of Depression

by William Yates, M.D. in Brain Posts

I had the opportunity to attend a presentation by Dr. Michael Irwin at the Warren Neuroscience Lecture Series in Tulsa, OK.Dr. Irwin has been a leader in research related to sleep disturbance, inflammation and depression risk. Here are my notes from the presentation and few related citations.Notes on Irwin PresentationDepression is important because it is prevalent, recurrent and often resistant to treatmentSleep disturbance is common as a symptom of depression, but also may be an independent modifiable risk factor for depressionSleep disturbance (deprivation) disrupts neuroimmune regulation via CRH/ACTH/Cortisol axis as well as the sympathetic nervous systemIndividuals with sleep complaints/disturbance show:Increased risk of depression recurrenceIncreased markers of inflammation including C-reactive protein, IL-6 levels, TNF levelsWomen appear more vulnerable to pro-inflammatory effects of sleep disruption Irwin and colleagues conducted research showing that administration of endotoxin produces acute inflammatory response but also:Acute increase in ratings of depressionIncreased sensitivity to negative social cuesDecreased sensitivity to positive social cuesAgain women were more sensitive to this adverse affective response to inflammationSo what is the take home message for clinicians?Sleep disturbance appears to increase risk for depression in women through an increase in signaling for inflammation with adverse brain effects.Sleep is important to monitor. This is especially true in women with a history of depression. Consider cognitive behavioral therapy (CBT) for insomnia. Additionally, other therapies may be helpful including Tai Chi and meditation. In a randomized controlled study, CBT treatment for insomnia in the elderly produced a sustained reduction in the inflammatory marker CRP while Tai Chi and control interventions did not.Readers with more interest in this topic are directed to the research citations by Dr. Irwin's team below.Photo of stained glass window from Prague, Czechoslovakia market is from the author's files.Follow the author on Twitter WRY999Slavich, G., & Irwin, M. (2014). From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychological Bulletin, 140 (3), 774-815 DOI: 10.1037/a0035302Lee E, Cho HJ, Olmstead R, Levin MJ, Oxman MN, & Irwin MR (2013). Persistent sleep disturbance: a risk factor for recurrent depression in community-dwelling older adults. Sleep, 36 (11), 1685-91 PMID: 24179302Inagaki TK, Muscatell KA, Irwin MR, Cole SW, & Eisenberger NI (2012). Inflammation selectively enhances amygdala activity to socially threatening images. NeuroImage, 59 (4), 3222-6 PMID: 22079507... Read more »

Slavich, G., & Irwin, M. (2014) From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychological Bulletin, 140(3), 774-815. DOI: 10.1037/a0035302

Lee E, Cho HJ, Olmstead R, Levin MJ, Oxman MN, & Irwin MR. (2013) Persistent sleep disturbance: a risk factor for recurrent depression in community-dwelling older adults. Sleep, 36(11), 1685-91. PMID: 24179302

Inagaki TK, Muscatell KA, Irwin MR, Cole SW, & Eisenberger NI. (2012) Inflammation selectively enhances amygdala activity to socially threatening images. NeuroImage, 59(4), 3222-6. PMID: 22079507

April 28, 2014
10:04 AM
515 views

Religion As A Suicide Protective Factor: Part I

by William Yates, M.D. in Brain Posts

Risk factors for suicide include male gender, older age, previous suicide attempts and presence of a mental disorder.Factors that reduce risk of suicide or provide a protective effect are less well understood.Two recent studies suggest religious belief and church attendance are linked to reduced risk of suicidal ideation and suicide attempts.Nicole Cushing and colleagues conducted a study of older adults suffering from depression.In this study, a series of subjects over 59 receiving outpatient or inpatient psychiatric services at Duke participated in an outcome study of geriatric depression.Four measures of religious involvement were assessed in the study with the following domains and questions:Public religious activity: "How often do you attend church or other religious meetings?"Religious importance: "Other than going to religious meetings, how important is religion to you?"Private religious practices: "How often do you spend time in private religious activities, such as prayer, meditation or bible study?"Private religious media involvement: "How often do you watch religious programs on the radio?"Subjects also were rated by a geriatric psychiatrist on severity of suicidal ideation in the last week on a 0 to 6 scale.Suicidal ideation was lowest in those subjects rating current physical health as high, church attendance as frequent and perception of social support as high.The authors noted that religion and church attendance may overlap with greater social support but using multivariate analysis they noted in the discussion:"..we found greater church attendance (i.e. public religious activity) above and beyond religious importance, private religious practice and measures of social support, was associated with less current suicidal ideation.."The authors note that depression may contribute to withdrawal from pleasurable social activities like attending church. They advise clinicians to encourage older depressed patients with church affiliation to reengage in church attendance and other activities providing social support.Suicidal ideation, suicide attempts and completed suicide are overlapping variables.In the next post, I will review a results from a large prospective study of completed suicide and religious belief including church attendance.Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of pelican at sunset is from the author's files.Follow the author on Twitter at WRY999Rushing NC, Corsentino E, Hames JL, Sachs-Ericsson N, & Steffens DC (2013). The relationship of religious involvement indicators and social support to current and past suicidality among depressed older adults. Aging & mental health, 17 (3), 366-74 PMID: 23121118... Read more »

Rushing NC, Corsentino E, Hames JL, Sachs-Ericsson N, & Steffens DC. (2013) The relationship of religious involvement indicators and social support to current and past suicidality among depressed older adults. Aging , 17(3), 366-74. PMID: 23121118

April 22, 2014
10:21 AM
552 views

Religious Belief Linked to Brain Cortex Thickness

by William Yates, M.D. in Brain Posts

In a previous post, I reviewed a longitudinal study of religious belief and major depression.This study by Lisa Miller and colleagues found a reduced risk of depression in subjects who rated religious belief or spirituality as an important factor in their lives.Reduction in depression risk with religiosity/spirituality was largest (90% smaller risk) in those with a family history of depression.This correlation may not be causal and may be explained by some common third factor between religion and depression.A recent study explored further a potential mechanism for a protective effect of religious belief/spirituality on depression risk.Miller further studied the cohort using brain magnetic resonance imaging (MRI) to estimate cortical structure volumes. Brain structure measures were compared in three groups of subjects:High stable: subjects reporting religion or spirituality as being of high importance on two separate ratings five years apartLow stable: subjects reporting religion or spirituality as being of low importance on two separate ratings five years apartUnstable: subjects with inconsistent ratings of the importance of religion or spiritualityThe key findings from this brain imaging study were:Subjects in the high stable group showed statistically thicker brain cortex measures in the left and right parietal lobes, left cuneus and precuneus regions and in the mesial frontal lobe of the right hemisphereHigh risk subjects (family history of depression) showed stronger effects of high religiosity/spirituality on cortical thickness and this was noted to be evident in the mesial frontal lobe regionsSubject ratings of depression severity at the time of imaging correlated inversely with temporal lobe brain cortex thickness The authors note the parietal cortex and cuneaus brain regions are involved in spatial processing, sensory processing, sense of self and reflective self-awareness.They summarize their study and implications with the following:"The importance of religion or spirituality therefore likely reinforces persons who are at greater familial and neuoranatomical risk for developing depression against actually becoming ill by providing reserve in the regions within the (depression) endophenotype.."This is an important study that is likely to lead to further structural and functional brain imaging research in risk and resilience to major depression. Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link in the citation below.Image of brain parietal lobe and cuneus regions is a screen shot from the iPad 3D Brain. 3D Brain is produced by the Cold Spring Harbor Laboratory DNA Learning Center with funding from the Dana Foundation and the William and Flora Hewlett Foundation.Follow the author on Twitter at WRY999Miller L, Bansal R, Wickramaratne P, Hao X, Tenke CE, Weissman MM, & Peterson BS (2014). Neuroanatomical correlates of religiosity and spirituality: a study in adults at high and low familial risk for depression. JAMA psychiatry, 71 (2), 128-35 PMID: 24369341... Read more »

Miller L, Bansal R, Wickramaratne P, Hao X, Tenke CE, Weissman MM, & Peterson BS. (2014) Neuroanatomical correlates of religiosity and spirituality: a study in adults at high and low familial risk for depression. JAMA psychiatry, 71(2), 128-35. PMID: 24369341

April 15, 2014
11:43 AM
468 views

Religious Belief and Depression Resilience

by William Yates, M.D. in Brain Posts

Identifying risk factors for brain disorders is a key element in clinical research.Understanding protective or resilience factors for brain disorders is also important and receiving increased attention in clinical research.Factors that promote resilience to brain disorders may come from a variety of domains. Religious belief is one domain receiving attention as a potential resilience factor.Miller and colleagues recently published a longitudinal study of religious belief and risk for major depression.The key elements of research design in their study included:Subjects: This study examined a cohort of young adults whose parents were identified as having a history of major depression (cases) or not having a parent with major depressionMeasures: Subjects received a structured interview for the presence of major depression at year 10 and year 20 in a 20-year follow-up study. Additionally, subjects were assessed for religiosity in three areas--"How important to you is religion or spirituality?" (rated on a one to four point scale), Frequency of attendance at a church, synagogue or other religious/spiritual services (rated on a five point scale), Current religion denomination affiliationStatistical Analysis: The key outcome variable was diagnosis of major depression between ages 10 and 20. Logistic regression analysis was used to assess the role of religious belief, church attendance and church affiliation on risk for major depression. Parental depression status (positive or negative for a history of parental depression) was examined as a moderator for effect of religionThe study found a significant association between religious belief and risk of major depression during followup. Subjects rating religion or spirituality as very importance was associated with a 90% reduction in depression risk during follow up in the high risk group (history of parental depression) and a 28% reduction in depression risk if they were in the low risk group (no history of parental depression).Higher frequency of church attendance was also associated with lower depression risk although not to a statistically significant level. Specific religious denominational affiliation did not appear to affect depression risk.The authors went on to note the association of high importance for religion/spirituality and lower depression risk seemed primarily through reduction in risk for recurrence of depression.This study is noteworthy for the large effect size on depression risk reduction. The authors note their findings support clinical assessment of religion/spirituality importance in clinical practice.Additionally, the authors note integrating religious/spiritual interventions in clinical management "may be useful for some patients". In my next post, I will review a brain imaging study involving this subject cohort with some interesting findings. Readers with more interest in this study can access the free full-text manuscript by clicking on the link below.Photo of willets on the beach is from the author's files.Follow the author on Twitter at WRY999Miller L, Wickramaratne P, Gameroff MJ, Sage M, Tenke CE, & Weissman MM (2012). Religiosity and major depression in adults at high risk: a ten-year prospective study. The American journal of psychiatry, 169 (1), 89-94 PMID: 21865527... Read more »

Miller L, Wickramaratne P, Gameroff MJ, Sage M, Tenke CE, & Weissman MM. (2012) Religiosity and major depression in adults at high risk: a ten-year prospective study. The American journal of psychiatry, 169(1), 89-94. PMID: 21865527

April 7, 2014
11:37 AM
467 views

The Genetics of Religious Belief

by William Yates, M.D. in Brain Posts

In the next few posts, I will review some of the recent brain-related research related to religious belief.Religious belief and religious affiliation run in families. This effect is not surprising as parents influence their children's type of religious experience during development.However, there is increasing evidence that adult religious belief and behavior is also influenced by genetic factors independent of family environment experience.Twin studies represent a powerful research model to tease out genetic from environmental influences. Twin studies exam differences in concordance rate between identical (monozygotic) and non-identical (dyzgotic) twins.Button and colleagues examined religious belief in a cohort of twins from the Community Twin Sample at the University of Colorado. This cohort was questioned about religious values in 5 domains by being asked the subjective importance of:Reliance on religious counsel or teaching when dealing with problemsBelief in GodReliance on religious beliefs as a daily living guideUse of prayer for facing personal problemsRegular religious attendanceTwins participating in the study were followed during adolescence and early adulthood. Different relative genetic influences were identified during the adolescent period compared to early adulthood. The key findings of the study included:The role of genetic influences on religious values and religious attendance increased during transition to adulthoodGenetic influences contributed to both religious belief and religious attendance during adulthoodTwo additional recent twin studies are informative on this topic.Hvidtjorn and colleagues examined the familial resemblance of religiousness in the Danish twin study. The key results from this study included:Monozygotic and dizygotic adolescent twins have high correlations on measures of religiousness supporting a strong shared environmental influencePersonal features of religiousness, eg belief in God were more influenced by genetic factors than social religious factors, eg church attendanceSome religious factors had higher genetic contributions with increasing ageFinally, Kandler and Riemann recently published results of a twin study examining religiousness that included a study of personality traits. The key findings from their study included:Religiousness was correlated with personality traits (agreeableness and openness to values)Family environmental effects on religiousness were strong during adolescence but waned during adulthoodGenetic influences and non-family environment contributed to measures of religiousness in adulthoodThe take home message from these studies is that genetic factors play a significant role in individual religious beliefs and behaviors. Shared environmental (familial) experiences have a key contribution during childhood and adolescence but wane over time.In upcoming posts, I will examine some of the studies linking religious belief with better health and longer life. Additionally, I will review some recent imaging studies of brain structure and function as they relate to religious belief.Readers with more interest in this topic are directed to the citations below.Follow the author on Twitter WRY999The diagram of DNA comes from the Wikipedia Commons Files and was authored by Medprime.Button TM, Stallings MC, Rhee SH, Corley RP, & Hewitt JK (2011). The etiology of stability and change in religious values and religious attendance. Behavior genetics, 41 (2), 201-10 PMID: 20711848 Hvidtjørn, D., Petersen, I., Hjelmborg, J., Skytthe, A., Christensen, K., & Hvidt, N. (2013). Familial Resemblance in Religiousness in a Secular Society: A Twin Study Twin Research and Human Genetics, 16 (02), 544-553 DOI: 10.1017/thg.2013.3 Kandler C, & Riemann R (2013). Genetic and environmental sources of individual religiousness: the roles of individual personality traits and perceived environmental religiousness. Behavior genetics, 43 (4), 297-313 PMID: 23681197... Read more »

Button TM, Stallings MC, Rhee SH, Corley RP, & Hewitt JK. (2011) The etiology of stability and change in religious values and religious attendance. Behavior genetics, 41(2), 201-10. PMID: 20711848

Hvidtjørn, D., Petersen, I., Hjelmborg, J., Skytthe, A., Christensen, K., & Hvidt, N. (2013) Familial Resemblance in Religiousness in a Secular Society: A Twin Study. Twin Research and Human Genetics, 16(02), 544-553. DOI: 10.1017/thg.2013.3

Kandler C, & Riemann R. (2013) Genetic and environmental sources of individual religiousness: the roles of individual personality traits and perceived environmental religiousness. Behavior genetics, 43(4), 297-313. PMID: 23681197

March 27, 2014
12:51 PM
433 views

Is Insomnia Relief Just a Mouse Click Away?

by William Yates, M.D. in Brain Posts

Cognitive behavioral treatment of insomnia (CBT-I) is increasingly recognized as an important treatment option.However, in some regions of the U.S. and the world, access to this type of therapy is limited and may be cost prohibitive.A recent review of the diagnosis and treatment of insomnia noted the promise of internet-based CBT-I. The promise of internet-based CBT-I is based on several randomized controlled trials.Ritterband and colleagues published a study 44 subjects randomized to internet-based CBT-I or a wait list. The primary outcome measure in this study was the Insomnia Severity Index. Subjects in the internet based CBT-I group experienced a statistically significant drop from a mean of 15.7 to 6.59 while there was no change in this measure in the wait list group.Espie and colleagues published a study of 164 adults in the United Kingdom recruited for a randomized study of internet based CBT-I compared to a imagery relief therapy (considered an insomnia placebo) and treatment as usual.In this UK study, sleep efficiency was identified as the primary outcome measure. Sleep efficiency is the total sleep time divided by the total time in bed. CBT-I proved superior to the other two treatment arms in this study by increasing sleep efficiency by 20% vs only 6% in each of the other two interventions.While researching this topic, I discovered several commercially available internet based CBT-I programs.One site, Sleep Healthy Using the Internet (SHUTi) appears to use one of the specific CBT-I protocols with some research support. The site offers an free insomnia score to see if CBT-I might be indicated. Individuals can self enroll in the SHUTi program for $129.50 allowing 16 weeks of access.I have no financial relationship with this site but will be interested in following the general acceptance and use of online based CBT-I. I would not be surprised if in the near future these sites are covered by insurance in a way similar to in person behavioral therapyThe SHUTi site notes the service is not a substitute for medical evaluation, advice, diagnosis, care or treatment. However, physicians might want to consider offering this option to patients as part of a comprehensive treatment and monitoring program.Readers with more interest in this topic can access the insomnia review and two clinical trials by clicking on the three PMID full access links in the citation below.If you have personally had experience with online CBT-I feel free to relate your experience in the comments.Follow the author on Twitter at WRY999Photo of zebra butterfly is from the author's files.Buysse DJ (2013). Insomnia. JAMA : the journal of the American Medical Association, 309 (7), 706-16 PMID: 23423416 Ritterband LM, Thorndike FP, Gonder-Frederick LA, Magee JC, Bailey ET, Saylor DK, & Morin CM (2009). Efficacy of an Internet-based behavioral intervention for adults with insomnia. Archives of general psychiatry, 66 (7), 692-8 PMID: 19581560... Read more »

Buysse DJ. (2013) Insomnia. JAMA : the journal of the American Medical Association, 309(7), 706-16. PMID: 23423416

Ritterband LM, Thorndike FP, Gonder-Frederick LA, Magee JC, Bailey ET, Saylor DK, & Morin CM. (2009) Efficacy of an Internet-based behavioral intervention for adults with insomnia. Archives of general psychiatry, 66(7), 692-8. PMID: 19581560

Espie CA, Kyle SD, Williams C, Ong JC, Douglas NJ, Hames P, & Brown JS. (2012) A randomized, placebo-controlled trial of online cognitive behavioral therapy for chronic insomnia disorder delivered via an automated media-rich web application. Sleep, 35(6), 769-81. PMID: 22654196

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